Duloxetine is marketed as duloxetine Hydrochloride under the trade name Cymbalta® by Eli Lilly. Chemically Duloxetine hydrochloride is (+)-(S)—N-methyl-γ-(1-naphthyloxy)2-thiophenepropylamine hydrochloride having structure of formula I. Cymbalta® is indicated for the acute and maintenance treatment of major depressive disorder, acute treatment of generalized anxiety disorder and for the management of neuropathic pain associated with diabetic peripheral neuropathy. It is also indicated for the management of fibromyalgia.
U.S. Pat. No. 5,023,269 discloses duloxetine and the pharmaceutically acceptable acid addition salts thereof.
U.S. Pat. No. 5,508,276 discloses formulation of duloxetine in the form of enteric pellets comprising hydroxypropylmethylcellulose acetate succinate.
U.S. Pat. No. 6,596,756 discloses a method of treating fibromyalgia by administering an effective amount of Duloxetine.
U.S. Patent Application No. 20060079569 discloses oral liquid composition consisting duloxetine or pharmaceutically acceptable derivatives thereof.
U.S. Patent Application No. 20070004795 discloses pharmaceutical composition comprising duloxetine or its pharmaceutically acceptable salts thereof and stabilizing amount of at least one buffering agent.
US Application No. 20060182796 discloses taste masked oral pharmaceutical composition containing a pharmaceutically active ingredient coated with a combination an enteric polymer and an ammonio methacrylate copolymer.
U.S. Application No. 20070149479 discloses nanoparticulate inclusion and charge complex, that comprises at least two complex partners, whereby a complex partner is an anionic inclusion-forming agent and another complex partner is a cationic active ingredient.
International (PCT) Application Publication No. WO2007034503A2 discloses controlled release dosage form of duloxetine comprising duloxetine or its pharmaceutically acceptable salts, pharmaceutically acceptable polymeric carrier and solubility enhancer.
International (PCT) Application Publication No. WO2009084017A2 discloses taste masked orally disintegrating tablet composition of memantine in combination with other active agents.
Duloxetine or pharmaceutically acceptable salts thereof are acid labile and degrade in acidic environment of gastrointestinal tract (GIT). Acid hydrolysis of its ether linkage results in 1-naphthol, which is known to be toxic and cause several side effects. Therefore, duloxetine or pharmaceutically acceptable salts thereof need protection from degradation in acidic environment of GIT. Such acid sensitive compounds have been formulated with enteric-coatings to protect them from degradation in stomach. The enteric-coated compositions of duloxetine or pharmaceutically acceptable salts thereof release the drug in lower part of GIT where pH is towards alkaline side. But such compositions result in a lag period from the time of administration of composition to the onset of therapeutic action.
Duloxetine or pharmaceutically acceptable salts thereof have low aqueous solubility and are slightly soluble in water. The low solubility results in practical difficulties in formulating such drugs for oral administration, particularly where early onset of therapeutic effect is desired or required.
Further, duloxetine or pharmaceutically acceptable salts thereof have pungent and bitter taste. In order to improve the acceptability and patient compliance it becomes necessary to mask the taste of such compounds. Thus, there is need to develop a taste masked pharmaceutical composition comprising duloxetine or pharmaceutically acceptable salts thereof having early onset of action with improved solubility.